Solid-phase synthesis of 4-triphenylphosphoranylidene-4,5-dihydropyrazol-5-ones, 4-aminocarbonyl-pyrroles, 4-methoxy-1H-pyrazol-5(2H)-ones and 2-thiazolin-4-ones from polymer-bound 1,2-diaza-1,3-butadienes

Article abstract of DOI:10.1016/S0040-4020(01)00523-3

The solid-phase synthesis of 4-triphenylphosphoranylidene-4,5-dihydropyrazol-5-ones, 4-aminocarbonyl-pyrroles, 4-methoxy-1H-pyrazol-5(2H)-ones and 2-thiazolin-4-ones using polymer-bound 1,2-diaza-1,3-butadienes is reported.

Full text of DOI:10.1016/S0040-4020(01)00523-3

TETRAHEDRON
Pergamon
Tetrahedron 57 +2001) 5855±5863
Solid-phase synthesis of 4-triphenylphosphoranylidene-4,5-
dihydropyrazol-5-ones, 4-aminocarbonyl-pyrroles,
4-methoxy-1H-pyrazol-5ꢀ2H)-ones and 2-thiazolin-4-ones from
polymer-bound 1,2-diaza-1,3-butadienes
Orazio A. Attanasi,a Lucia De Crescentini,a Paolino Filippone,a,p Fabio Mantellinia
and Lutz F. Tietzeb
a
Á
Istituto di Chimica Organica, Universita di Urbino, Piazza della Repubblica 13, 61029 Urbino, Italy
È È È È
Institut fur Organische Chemie, Georg-August-Universitat Gottingen, Tammannstr. 2, D-37077 Gottingen, Germany
b
Received 29 December 2000; revised 20 April 2001; accepted 10 May 2001
AbstractÐThe solid-phase synthesis of 4-triphenylphosphoranylidene-4,5-dihydropyrazol-5-ones, 4-aminocarbonyl-pyrroles, 4-methoxy-
1H-pyrazol-5+2H)-ones and 2-thiazolin-4-ones using polymer-bound 1,2-diaza-1,3-butadienes is reported. q 2001 Elsevier Science Ltd. All
rights reserved.
1.Introduction
increasing attention is currently devoted to this technique.2
Some of us previously reported the use of modi®ed
Merri®eld resin in the preparation of polymer-bound
b-dicarbonyl derivatives from which some heterocyclic
products were obtained.3 Since 1,2-diaza-1,3-butadienes
Combinatorial synthesis of small organic molecules has
evolved rapidly in the last few years to become a new
paradigm for contemporary drug discovery.1 For this reason,
Scheme 1.
Keywords: diaza compounds; Wang resin; pyrroles; pyrazol-5-ones; thiazolin-4-ones.
Corresponding author. Fax: 139-0722-2907; e-mail: attanasi@uniurb.it
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+01)00 523-3

5856
O. A. Attanasi et al. / Tetrahedron 57 12001) 5855±5863
Table 1. Polymer-bound 1,2-diaza-1,3-butadienes 5a±j
Both resins were treated with tert-butyl acetoacetate
+toluene, re¯ux, 3 h) to give the polymer-bound
b-ketoesters 1a±b, in accordance with Witzeman's
method.9 Reaction of polymer-bound b-ketoesters 1a±b
with hydrazine derivatives 2a±e +10equiv., DMF or THF,
room temperature, 4 h) led to corresponding hydrazones
3a±j that were subjected to bromination with phenyl-
trimethylammonium tribromide10 +PTAB) +1 equiv.,
dichloromethane +DCM), room temperature, 3 h) affording
brominated hydrazones 4a±j. Treatment of these
compounds with N,N-diisopropylethylamine +DIPEA)
+2 equiv., DCM, room temperature, 5 min) provided
polymer-bound 1,2-diaza-1,3-butadienes 5a±j +Scheme 1
and Table 1).
1
a
2
a
R1
3,4,5
R1
NH2
a
NH2
b
b
c
NHPh
OMe
OEt
b
c
d
e
f
NHPh
Ot-Bu
OEt
d
e
Ot-Bu
OMe
NH2
g
h
i
NHPh
Ot-Bu
OEt
Addition of triphenylphosphine +10equiv., AcOEt, room
temperature, 1 h) to modi®ed Merri®eld resin polymer-
bound 1,2-diaza-1,3-butadienes 5a±e produced the
corresponding 1,5-zwitterionic intermediates 6a±e. In
turn, they cyclize and then release 1-substituted 8a±e and
1-unsubstituted 4-triphenylphosphoranylidene-4,5-dihydro-
pyrazol-5-ones 9 into solution by methanolysis +MeOH,
re¯ux, 10±12 h) through the betaine form 7 +Scheme 2).
The reactions with triphenylphosphine were carried out
also using Wang resin polymer-bound 1,2-diaza-1,3-buta-
dienes 5f±j to achieve the same ®nal products 8a±e and 9
derived from 1,5-zwitterionic intermediates 6f±j with
comparable yields and reaction times. The overall yields
of these solid-phase reactions are comparable with the
corresponding reactions in solution +Table 2).11
j
OMe
showed to be useful building blocks in organic
chemistry,4±7 we reported in a preliminary publication on
the construction of modi®ed Merri®eld resin polymer-
bound 1,2-diaza-1,3-butadiene derivatives from which
some 4-triphenylphosphoranylidene-4,5-dihydropyrazol-5-
ones were obtained.8 Here in this report, we described an
easy protocol for the synthesis of 4-aminocarbonylpyrroles,
4-methoxy-1H-pyrazol-5+2H)-ones, and 2-thiazolin-4-ones
using modi®ed Merri®eld and Wang resin.
Wang resin polymer-bound 1,2-diaza-1,3-butadienes 5f±h
and b-ketoamides 10a±d +10equiv., THF, room tempera-
ture, 4 h) in the presence of catalytic amounts of copper+II)
dichloride gave polymer-bound 4-aminocarbonylpyrroles
13a±l. In accordance with our previous ®ndings, the nucleo-
philic attack of an activated methylene group on the 1,2-
diazaheterodiene moiety in 5f±h affords the 1,4-adduct 11
as an intermediate. This Michael-type addition is followed
by an intramolecular addition of the nitrogen atom of the
CvN group to the carbonyl group in d position yielding the
pyrroles 13a±l. These reactions proceed smoothly under
2.Results and discussion
Commercially available Merri®eld resin was modi®ed by
introduction of a spacer with a free hydroxyl group to
enhance reactivity of the substrates bound to the polymer.3a
In connection with our ongoing investigations we found
that commercial Wang resin can also be used with
comparable ef®ciency and yields instead of the modi®ed
Merri®eld one.
Scheme 2.

O. A. Attanasi et al. / Tetrahedron 57 12001) 5855±5863
5857
Table 2. Yields and reaction times of 4-triphenylphosphoranylidene-4,5-dihydropyrazol-5-ones 8a±e and 9a
5,6
R1
8
a
R1
Yields 819a,b,c +%)
Yields 819a,b,d +%)
Reaction time +h)e
1.011.0
Re¯ux time +h)f
a
NH2
NH2
42
41
b
c
d
e
f
NHPh
Ot-Bu
OEt
b
c
NHPh
Ot-Bu
OEt
36
18
12
17
3.40
21
13
18
1.010
1.012.0
1.012.0
1.011.0
d
e
OMe
NH2
OMe
g
h
i
NHPh
Ot-Bu
OEt
j
OMe
a
Overall yields for the multi-step process of isolated 8 and 9 in respect to the starting tert-butyl acetoacetate.
Ratio 8:9 nearly 1:1.
Yields obtained using modi®ed Merri®eld resin.
Yields obtained using Wang resin.
Reaction times are the same using modi®ed Merri®eld and Wang resins.
Re¯ux times are the same using modi®ed Merri®eld and Wang resins.
b
c
d
e
f
Scheme 3.
Table 3. Yields and reaction times of 4-aminocarbonyl-pyrroles 14a±l
5
R1
10
R2
R3
13, 14
R1
R2
R3
Yields 14a +%)
Reaction time +h)
Re¯ux time +h)
2.0
f
g
h
NH2
NHPh
Ot-Bu
a
b
c
Ph
Me
Me
Me
Ph
a
b
c
d
e
f
g
h
i
NH2
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
64
45
22
59
35
19
44
36
19
72
37
17
4.5
p-Cl±Ph
p-MeO±Ph
Ph
NHPh
Ot-Bu
NH2
NHPh
Ot-Bu
NH2
NHPh
Ot-Bu
NH2
NHPh
Ot-Bu
4.04.0
3.03.0
5.02.5
4.5
4.04.0
5.03.0
3.03.0
3.5
d
p-Cl±Ph
p-Cl±Ph
p-Cl±Ph
p-MeO±Ph
p-MeO±Ph
p-MeO±Ph
Ph
3.0
2.0
4.0
j
k
l
4.5
4.03.5
5.03.5
Ph
Ph
Ph
Ph
a
Overall yields for the multi-step process of isolated 14a±l in respect to the starting tert-butyl acetoacetate.

5858
O. A. Attanasi et al. / Tetrahedron 57 12001) 5855±5863
Scheme 4.
the azo±ene system. Then the intramolecular nucleophilic
attack of the NH hydrazonic nitrogen atom at the alkoxy-
carbonyl group results in the pyrazole ring closure with loss
of an alcohol molecule +Scheme 4). The overall yields of
these solid-phase reactions are again comparable with the
corresponding reactions in solution +Table 4).15
Table 4. Yields and reaction times of 4-methoxy-1H-pyrazol-5+2H)-ones
16a±c
5
16
R1
Yieldsa +%)
Reaction time +h)
f
g
h
a
b
c
NH2
NHPh
Ot-Bu
37
42
9
3.0
3.5
5.0
Addition of thiobenzamide +10equiv., MeOH, room
temperature, 3 h) to Wang resin polymer-bound 1,2-diaza-
1,3-butadienes 5f±h afforded 2-thiazolin-4-ones 18a±c.
The reaction clearly proceeds with the formation of 1,4-
a
Overall yields for the multi-step process of isolated 16a±c in respect to
the starting tert-butyl acetoacetate.
Scheme 5.
adduct intermediates via SH nucleophilic attack of the
thioloimido function to the terminal carbon atom of the
heterodiene system bearing a carboxylate group, on which
a subsequent intramolecular NH nucleophilic attack with
loss of an alcohol molecule leads to the thiazolinone ring
closure +Scheme 5). The overall yields of these solid-phase
reactions are comparable with the corresponding reactions
in solution +Table 5).16
Table 5. Yields and reaction times of 2-thiazolin-4-ones 18a±c
5
18
R1
Yieldsa +%)
Reaction time +h)
f
g
h
a
b
c
NH2
NHPh
Ot-Bu
42
403.0
11
2.0
3.0
a
Overall yields for the multi-step process of isolated 18a±c in respect to
the starting tert-butyl acetoacetate.
3.Conclusion
copper+II) ion catalysis. The polymer-bound 4-amino-
carbonylpyrroles 13a±l were cleaved from the resin by
re¯ux +3 h) in MeOH±THF +1:4) in the presence of sodium
methoxide +2 equiv.)12 to give the 4-aminocarbonylpyrroles
14a±l +Scheme 3). The overall yields of these solid-phase
reactions are comparable with the corresponding reactions
in solution +Table 3).13±14
In conclusion, this paper describes a general protocol for the
preparation of different polymer-bound 1,2-diaza-1,3-buta-
dienes which are valuable substrates in synthetic organic
chemistry. The mild and simple conditions of this procedure
permit access to valuable combinatorial libraries. In fact,
many cyclic compounds previously obtained in solution
from these reagents may now be reached by solid-
phase reactions. The synthesis of some 4-triphenyl-
phosphoranylidene-4,5-dihydropyrazol-5-ones, 4-amino-
carbonyl-pyrroles, 4-methoxy-1H-pyrazol-5+2H)-ones and
2-thiazolin-4-ones represents an example of such an
application. With the exception of the cleavage steps, the
reactions occur at room temperature, with formation of
only minor by-products and simple manipulation of the
Sodium methoxide +2 equiv., MeOH/THF 1:4, room
temperature, 3 h) readily reacted with Wang resin polymer-
bound 1,2-diaza-1,3-butadienes 5f±h, affording a-methoxy-
hydrazones 15a±c that, in the presence of a second
equivalent of sodium methoxide produced 4-methoxy-1H-
pyrazol-5+2H)-ones 16a±c. The ®rst step of the reaction
consists of a 1,4-addition of the nucleophilic reagent to

O. A. Attanasi et al. / Tetrahedron 57 12001) 5855±5863
5859
reaction mixtures solely by ®ltration. The mild conditions
of this reaction sequence makes it well amenable for
automation.
4.3. General procedure for the synthesis of 1-substituted
8a±e and 1-unsubstituted 4-triphenylphosphor-
anylidene-4,5-dihydropyrazol-5-ones 9
To polymer-bound 1,2-diaza-1,3-butadienes 5a±j in AcOEt
+7 ml) +10equiv.) triphenylphosphine was added under
magnetic stirring. The reaction was allowed to stand at
room temperature for 1 h obtaining the polymer-bound
1,5-zwitterionic intermediates 6a±j, that were washed
with DMF, AcOEt, MeOH +3£5 ml). Products 6a±j in
MeOH +10ml) were re¯uxed under magnetic stirring for
10±12 h obtaining 1-substituted 8a±e and 1-unsubstituted
4-triphenylphosphoranylidene-4,5-dihydropyrazol-5-ones 9
by ®ltration in MeOH solution +.12±42%, using Merri®eld
resin; .13±41%, using Wang resin). After evaporation of
the washing solvent under reduced pressure, the products
were obtained by crystallization from ethyl acetate/
petroleum ether +40±608C). The ®nal products 8a±e and 9
were compared with authentic specimens by means of
chromatographic and spectroscopic techniques +TLC, IR,
NMR, MS).11
4.Experimental
4.1. General
tert-Butyl acetoacetate, semicarbazide hydrochloride,
sodium acetate, methyl carbazate, ethyl carbazate, tert-
butyl carbazate, phenyltrimethylammonium tribromide,
triphenylphosphine,
acetoacetanilide,
40-chloroaceto-
acetanilide, p-acetoacetanisidide, 2-benzoylacetanilide,
sodium methoxide and thiobenzamide were commercial
materials and were used without further puri®cation.
Solvents were purchased and used without further puri®ca-
tion with the exception of THF which was distilled from
sodium hydroxide. Melting points were determined in open
capillary tubes and are uncorrected. IR-FT spectra were
obtained as Nujol mulls. Mass spectra were made at an
ionizing voltage of 70eV. All 1H-NMR and 13C-NMR
spectra were recorded at 400 and 100.56 MHz, respectively.
Chemical shifts +dH) are reported relative to TMS as internal
standard. All coupling constants +J) values are given in Hz.
Chemical shifts +dC) are reported relative to DMSO-d6 or
CDCl3 as internal standard in a broad band decoupled mode;
the multiplicities were obtained by using 135 and 908 DEPT
experiments to aid in assignment +qˆmethyl, tˆmethylene,
dˆmethyne, sˆquaternary). The abbreviations used are as
follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multi-
plet; br, broad; D2O exch., exchanged with D2O. Precoated
silica gel plates 0.25 mm were employed for analytical thin
layer chromatography and silica gel 35±70 m for column
chromatography.
4.3.1. Compound 8a. White powder from ethyl acetate/
petroleum ether +40±608C); mp 336±3378C; IR: nmax
3515, 3310, 1715, 1620 cm21; dH +CDCl3) 1.41 +3H, s,
CH3), 5.18 +2H, br s, NH2, D2O exch.), 7.55±7.74 +15H,
1
m, aromatic); dC +CDCl3) 16.1 +q), 122.4 +s, JCPˆ
2
1
92.6 Hz), 129.8 +d, JCPˆ10.6 Hz), 132.7 +s, JCPˆ
3
110.0 Hz), 134.0 +d), 134.2 +d, JCPˆ10.8 Hz), 151.6 +s,
2JCPˆ11.4 Hz), 152.7 +s), 169.0+s, JCPˆ18.2 Hz); MS:
2
m/z +%) 401 +2) [M1], 357 +100). Anal. Calcd for
C23H20N3O2P: C, 68.82; H, 5.02; N, 10.47. Found: C,
68.91; H, 5.13; N, 10.36.
4.3.2. Compound 8b. White powder from ethyl acetate/
petroleum ether +40±608C); mp 273±2758C; IR: nmax
3410, 1715, 1630 cm21; dH +DMSO-d6) 1.24 +3H, s, CH3),
7.02 +1H, t, Jˆ7.6 Hz, aromatic), 7.28 +2H, t, Jˆ7.6 Hz,
aromatic), 7.48 +2H, d, Jˆ7.6 Hz, aromatic), 7.66±7.82
+15H, m, aromatic), 11.54 +1H, s, NH, D2O exch.); dC
+DMSO-d6) 16.0+q), 118.0+d), 119.9 +d), 122.4 +s,
4.2. General procedure for the synthesis of polymer-
bound hydrazones 3a±j, a-bromohydrazones 4a±j, 1,2-
diaza-1,3-butadienes 5a±j
2
1JCPˆ92.6 Hz), 123.7 +d), 129.6 +s), 130.4 +d, JCPˆ
1
3
Hydrazines 2a±e +10equiv.) were added to a magnetically
stirred mixture of polymer-bound b-ketoester 1a +0.300 g,
0.7 mmol per gram of resin) or 1b +0.300 g, 1.2 mmol per
gram of resin) in DMF +7 ml) in the case of hydrazines 2a±b
or THF in the case of hydrazines 2c±e. The semicarbazide
hydrochloride 2a was treated with an equimolecular
amount of sodium acetate to give the free form. The
reaction was allowed to stand at room temperature for 4 h
obtaining 3a±j. The polymer-bound hydrazones 3a±j were
washed with MeOH, THF, DCM +3£5 ml). To polymer-
bound hydrazones 3a±j in DCM +150ml) PTAB
+1 equiv.) was added portionwise with magnetic stirring.
The reaction was allowed to stand at room temperature for
3 h obtaining 4a±j. The polymer-bound a-bromohydra-
zones 4a±j were washed with MeOH and DCM +3£5 ml).
To polymer-bound a-bromohydrazones 4a±j in DCM
+7 ml) was added under magnetic stirring DIPEA
+2 equiv.). The reaction was allowed to stand at room
temperature for 5 min obtaining 5a±j. The polymer-bound
1,2-diaza-1,3-butadienes 5a±j were washed with THF and
DCM +3£5 ml)
12.9 Hz), 133.7 +s, JCPˆ102.0 Hz), 134.6 +d, JCPˆ
2
10.6 Hz), 135.1 +d), 138.9 +s), 151.6 +s, JCPˆ12.1 Hz),
169.0+s, JCPˆ19.0Hz); MS: m/z +%) 477 +2) [M1], 357
2
+100). Anal. Calcd for C29H24N3O2P: C, 72.95; H, 5.07; N,
8.80. Found: C, 72.91; H, 5.15; N, 8.77.
4.3.3. Compound 8c. White powder from ethyl acetate/
petroleum ether +40±608C); mp 334±3368C; IR: nmax
1745, 1615 cm21; dH +DMSO-d6) 1.15 +3H, s, CH3), 1.45
+9H, s, CO2t-Bu), 7.62±7.75 +15H, m, aromatic); dC
+DMSO-d6) 14.8 +q), 28.6 +q), 81.3 +s), 123.1 +s,
1JCPˆ92.0Hz), 130.1 +d,
2JCPˆ12.0Hz), 133.5 +s,
3
1JCP2ˆ102.0 Hz), 134.3 +d), 134.5 +d, JCPˆ10.6 Hz), 151.4
2
+s, JCPˆ12.2 Hz), 159.1 +s), 168.0+s, JCPˆ19.0Hz); MS:
m/z +%) 458 +1) [M1], 357 +100). Anal. Calcd for
C27H27N2O3P: C, 70.73; H, 5.94; N, 6.11. Found: C,
70.83; H, 5.87; N, 6.23.
4.3.4. Compound 8d. White powder from ethyl acetate/
petroleum ether +40±608C); mp 227±2308C; IR: nmax
1745, 1625 cm21; dH +DMSO-d6) 1.19 +3H, s, CH3), 1.67

5860
O. A. Attanasi et al. / Tetrahedron 57 12001) 5855±5863
+3H, t, Jˆ7.0Hz, CO 2CH2CH3), 4.50+2H, q, Jˆ7.0Hz,
CO2CH2CH3), 7.65±7.85 +15H, m, aromatic); dC +DMSO-
aromatic), 9.30+1H, br s, NH, D O exch.), 10.26 +1H, br
2
s, NH, D2O exch.); dC +DMSO-d6) 10.4 +q), 11.2 +q), 51.6
+q), 107.6 +s), 116.8 +s), 120.2 +d), 123.6 +d), 129.0 +d),
132.5 +s), 136.4 +s), 140.2 +s), 157.4 +s), 163.7 +s), 165.7
+s); MS: m/z +%) 330+24) [M 1], 313 +7), 238 +100). Anal.
Calcd for C16H18N4O4: C, 58.16; H, 5.50; N, 16.97. Found:
C, 58.32; H, 5.61; N, 16.88.
1
d6) 11.9 +q), 14.7 +q), 62.1 +t), 123.0+s, JCPˆ92.2 Hz),
2
1
129.9 +d, JCP3ˆ11.8 Hz), 133.7 +s, JCPˆ102.0 Hz), 134.3
+d), 135.0+d, JCPˆ10.4 Hz), 151.4 +s, 2JCPˆ12.0Hz), 159.5
+s), 168.2 +s, 2JCPˆ19.0Hz); MS: m/z +%) 430+1) [M 1], 357
+100). Anal. Calcd for C25H23N2O3P: C, 69.76; H, 5.39; N,
6.51. Found: C, 69.70; H, 5.51; N, 6.58.
4.4.2. Compound 14b. White powder from ethyl acetate/
petroleum ether +40±608C); mp 228±2308C; IR: nmax 3300,
3210, 1690, 1655, 1630 cm21; dH +DMSO-d6) 2.16 +3H, s,
CH3), 2.34 +3H, s, CH3), 3.65 +3H, s, CO2CH3), 6.97±7.02
+2H, m, aromatic), 7.25±7.29 +4H, m, aromatic), 7.45 +2H,
d, Jˆ7.6 Hz, aromatic), 7.67 +2H, d, Jˆ7.6 Hz, aromatic),
9.34 +1H, br s, NH, D2O exch.), 9.53 +1H, br s, NH, D2O
exch.), 10.21 +1H, br s, NH, D2O exch.); dC +DMSO-d6)
10.5 +q), 11.4 +q), 51.5 +q), 107.8 +s), 116.2 +s), 119.5 +d),
119.8 +d), 122.9 +d), 123.4 +d), 129.2 +d), 129.5 +d), 130.4
+s), 133.5 +s), 136.5 +s), 139.6 +s), 154.5 +s), 164.4 +s), 165.1
+s); MS: m/z +%) 406 +12) [M1], 314 +100). Anal. Calcd for
C22H22N4O4: C, 65.01; H, 5.46; N, 13.78. Found: C, 65.22;
H, 5.40; N, 13.62.
4.3.5. Compound 8e. White powder from ethyl acetate/
petroleum ether +40±608C); mp 231±2338C; IR: Imax
1750, 1630 cm21; dH +DMSO-d6) 1.18 +3H, s, CH3), 3.51
+3H, s, CO2CH3), 7.60±7.73 +15H, m, aromatic); dC
1
+DMSO-d6) 14.6 +q), 53.6 +q), 122.6 +s, JCPˆ92.0Hz),
2
1
129.4 +d, JCPˆ12.0Hz), 133.3 +s, JCPˆ102.0 Hz), 134.4
+d), 134.8 +d, 3JCPˆ10.6 Hz), 151.7 +s, 2JCPˆ12.2 Hz), 159.8
2
+s), 168.0+s, JCPˆ19.0Hz); MS: m/z +%) 416 +4) [M1], 357
+100). Anal. Calcd for C24H21N2O3P: C, 69.22; H, 5.05; N,
6.73. Found: C, 69.31; H, 5.15; N, 6.81.
4.3.6. Compound 9. White powder from ethyl acetate/
petroleum ether +40±608C); mp 336±3388C; IR: nmax
3210, 3130, 1600 cm21; dH +DMSO-d6) 1.38 +3H, s, CH3),
7.42±8.03 +16H, m, aromatic and NH, D2O exch.); dC
4.4.3. Compound 14c. White powder from ethyl acetate/
petroleum ether +40±608C); mp 188±1908C; IR: nmax 3300,
1735, 1700, 1665 cm21; dH +DMSO-d6) 1.36 +9H, s, CO2t-
1
+DMSO-d6) 15.9 +q), 123.0+s, JCPˆ92.6 Hz), 130.2 +d,
1
2JCPˆ11.6 Hz), 132.8 +s, JCPˆ108.0 Hz), 133.8 +d), 134.3
3
2
+d, JCPˆ10.4 Hz), 151.4 +s, JCPˆ12.0Hz), 168.8 +s,
2JCPˆ18.8 Hz); MS: m/z +%) 358 +89) [M1], 357 +100).
Anal. Calcd for C22H19N2OP: C, 73.73; H, 5.34; N, 7.82.
Found: C, 73.81; H, 5.51; N, 7.73.
Bu), 2.14 +3H, s, CH3), 2.30+3H, s, CH ), 3.65 +3H, s,
3
CO2CH3), 7.02 +1H, t, Jˆ7.6 Hz, aromatic), 7.26 +2H, t,
Jˆ7.6 Hz, aromatic), 7.66 +2H, d, Jˆ7.6 Hz, aromatic),
10.13 +1H, s, NH, D2O exch.), 10.52 +1H, br s, NH, D2O
exch.); dC +DMSO-d6) 10.2 +q), 11.0 +q), 28.3 +q), 51.7 +q),
81.7 +s), 108.0 +s), 116.6 +s), 120.1 +d), 123.6 +d), 129.2 +d),
131.7 +s), 136.0+s), 140.4 +s), 156.3 +s), 164.1 +s), 165.4 +s);
MS: m/z +%) 387 +61) [M1], 295 +89), 269 +100). Anal.
Calcd for C20H25N3O5: C, 61.99; H, 6.51; N, 10.85.
Found: C, 61.78; H, 6.31; N, 10.91.
4.4. General procedure for the synthesis of 4-amino-
carbonyl-pyrroles 14a±l
In the presence of a catalytic amount of copper+II) chloride
+0.5 equiv.) b-ketoamides 10a±d +10equiv.) were added to
polymer-bound 1,2-diaza-1,3-butadienes 5f±h in THF
+7 ml) under magnetic stirring. The reaction was allowed
to stand at room temperature for 3±5 h obtaining 13a±l
that were washed with MeOH, THF and DCM +3£5 ml).
In the presence of sodium methoxide +2 equiv.) in
MeOH±THF +2:8 ml)12 the polymer-bound 4-amido-
pyrroles 13a±l were re¯uxed, under magnetic stirring, for
2±4 h obtaining by ®ltration 4-aminocarbonyl-pyrroles
14a±l in solution +.17±72%). The residue resin was
washed with MeOH and THF +3£5 ml). The solvent
was removed in vacuo, and the residue, dissolved in
MeOH, was treated, under magnetic stirring, with
Amberlyst 15-H. The reaction was allowed to stand at
room temperature for 1 h obtaining 14a±l. After evapora-
tion of the washing solvents under reduced pressure
products 14a±l were obtained by crystallization from
ethyl acetate/petroleum ether +40±608C). The ®nal products
14a±l were compared with authentic specimens by means of
chromatographic and spectroscopic techniques +TLC, IR,
NMR, MS).13,14
4.4.4. Compound 14d. White powder from ethyl acetate/
petroleum ether +40±608C); mp 298±2998C; IR: nmax 3425,
3275, 3210, 1680, 1660, 1630 cm21; dH +DMSO-d6) 2.13
+3H, s, CH3), 2.29 +3H, s, CH3), 3.63 +3H, s, CO2CH3), 6.29
+2H, br s, NH2, D2O exch.), 7.33 +2H, d, Jˆ8.4 Hz,
aromatic), 7.69 +2H, d, Jˆ8.4 Hz, aromatic), 9.30+1H, br
s, NH, D2O exch.), 10.29 +1H, br s, NH, D2O exch.); dC
+DMSO-d6) 10.5 +q), 11.3 +q), 51.7 +q), 107.4 +s), 115.7
+s), 121.4 +d), 127.0+s), 129.1 +d), 132.9 +s), 137.1 +s),
139.4 +s), 157.5 +s), 164.4 +s), 165.6 +s); MS: m/z +%) 366
+12) [M1 12], 364 +32) [M1], 238 +100). Anal. Calcd for
C16H17N4O4Cl: C, 52.68; H, 4.70; N, 15.36. Found: C,
52.49; H, 4.81; N, 15.41.
4.4.5. Compound 14e. White powder from ethyl acetate/
petroleum ether +40±608C); mp 220±2228C; IR: nmax 3300,
3250, 3205, 1690, 1650, 1625 cm21; dH +DMSO-d6) 2.17
+3H, s, CH3), 2.35 +3H, s, CH3), 3.63 +3H, s, CO2CH3), 6.99
+1H, t, Jˆ7.6 Hz, aromatic), 7.27 +2H, t, Jˆ7.6 Hz,
aromatic), 7.33 +2H, d, Jˆ8.8 Hz, aromatic), 7.46 +2H, d,
Jˆ7.6 Hz, aromatic), 7.73 +2H, d, Jˆ8.8 Hz, aromatic), 9.28
+1H, s, NH, D2O exch.), 9.51 +1H, s, NH, D2O exch.), 10.32
+1H, s, NH, D2O exch.); dC +DMSO-d6) 10.5 +q), 11.3 +q),
51.6 +q), 107.8 +s), 116.0 +s), 119.6 +d), 121.3 +d), 123.2 +s),
126.9 +d), 129.1 +d), 129.4 +d), 132.6 +s), 137.0+s), 139.5 +s),
139.8 +s), 154.4 +s), 164.5 +s), 165.0+s); MS: m/z +%) 442 +3)
4.4.1. Compound 14a. White powder from ethyl acetate/
petroleum ether +40±608C); mp 242±2458C; IR: nmax 3395,
3250, 3195, 1710, 1655 cm21; dH +DMSO-d6) 2.14 +3H, s,
CH3), 2.35 +3H, s, CH3), 3.67 +3H, s, CO2CH3), 6.28 +2H, br
s, NH2, D2O exch.), 7.00 +1H, t, Jˆ7.6 Hz, aromatic), 7.28
+2H, t, Jˆ7.6 Hz, aromatic), 7.67 +2H, d, Jˆ7.6 Hz,

O. A. Attanasi et al. / Tetrahedron 57 12001) 5855±5863
5861
[M112], 440+10) [M 1], 328 +59), 314 +100). Anal. Calcd
for C22H21N4O4Cl: C, 59.93; H, 4.80; N, 12.71. Found: C,
59.88; H, 4.88; N, 12.83.
petroleum ether +40±608C); mp 237±2388C; IR: nmax 3435,
3275, 3220, 1730, 1680, 1640 cm21; dH +DMSO-d6) 2.36
+3H, s, CH3), 3.62 +3H, s, CO2CH3), 6.18 +2H, s, NH2, D2O
exch.), 6.98 +1H, t, Jˆ7.6 Hz, aromatic), 7.20±7.36 +5H, m,
aromatic), 7.44 +2H, d, Jˆ7.6 Hz, aromatic), 7.53 +2H, d,
Jˆ7.6 Hz, aromatic), 9.36 +1H, s, NH, D2O exch.), 10.05
+1H, br s, NH, D2O exch.); dC +DMSO-d6) 11.2 +q), 51.7 +q),
108.2 +s), 119.1 +s), 120.1 +d), 123.6 +s), 123.7 +d), 128.5 +d),
128.6 +d), 129.1 +d), 130.1 +d), 132.4 +s), 137.7 +s), 140.3 +s),
157.6 +s), 164.6 +s), 164.8 +s); MS: m/z +%) 392 +10) [M1],
300 +100). Anal. Calcd for C21H20N4O4: C, 64.28; H, 5.14;
N, 14.28. Found: C, 64.35; H, 5.07; N, 14.31.
4.4.6. Compound 14f. White powder from ethyl acetate/
petroleum ether +40±608C); mp 198±2008C; IR: nmax
3310, 3180, 1755, 1690, 1665 cm21; dH +DMSO-d6) 1.37
+9H, s, CO2t-Bu), 2.11 +3H, s, CH3), 2.29 +3H, s, CH3), 3.62
+3H, s, CO2CH3), 7.34 +2H, d, Jˆ8.8 Hz, aromatic), 7.69
+2H, d, Jˆ8.8 Hz, aromatic), 10.25 +1H, s, NH, D2O exch.),
10.72 +1H, br s, NH, D2O exch.); dC +DMSO-d6) 10.2 +q),
11.0+q), 28.3 +q), 51.7 +q), 81.3 +s), 108.0+s), 116.3 +s),
121.4 +d), 127.1 +s), 129.1 +d), 131.6 +s), 136.1 +s), 139.4 +s),
156.4 +s), 164.2 +s), 165.1 +s); MS: m/z +%) 423 +3) [M1
12], 421 +11) [M1], 360+4), 358 +13), 347 +4), 345 +13),
293 +100). Anal. Calcd for C20H24N3O5Cl: C, 56.99; H, 5.74;
N, 9.98. Found: C, 56.77; H, 5.81; N, 10.01.
4.4.11. Compound 14k. White powder from ethyl acetate/
petroleum ether +40±608C); mp 244±2468C; IR: nmax 3380,
3270, 3200, 1720, 1695, 1645 cm21; dH +DMSO-d6) 2.43
+3H, s, CH3), 3.64 +3H, s, CO2CH3), 6.96±7.58 +15H, m,
aromatic), 9.17 +1H, br s, NH, D2O exch.), 9.56 +1H, s, NH,
D2O exch.), 10.13 +1H, s, NH, D2O exch.); dC +DMSO-d6)
11.2 +q), 51.7 +q), 108.4 +s), 119.2 +s), 119.4 +d), 120.1 +d),
123.1 +d), 123.7 +s), 128.6 +d), 128.7 +d), 129.2 +d), 129.5
+d), 130.1 +d), 130.3 +d), 132.6 +s), 137.8 +s), 139.8 +s), 140.3
+s), 154.7 +s), 164.5 +s), 164.8 +s); MS: m/z +%) 468 +15)
[M1], 376 +100). Anal. Calcd for C27H24N4O4: C, 69.20; H,
5.17; N, 11.96. Found: C, 69.21; H, 5.23; N, 11.78.
4.4.7. Compound 14g. White powder from ethyl acetate/
petroleum ether +40±608C); mp 253±2558C; IR: nmax 3395,
3250, 3190, 1690, 1645 cm21; dH +DMSO-d6) 2.14 +3H, s,
CH3), 2.29 +3H, s, CH3), 3.65 +3H, s, CO2CH3), 3.71 +3H, s,
OCH3), 6.28 +2H, s, NH2, D2O exch.), 6.86 +2H, d,
Jˆ8.4 Hz, aromatic), 7.57 +2H, d, Jˆ8.4 Hz, aromatic),
9.28 +1H, s, NH, D2O exch.), 10.04 +1H, s, NH, D2O
exch.); dC +DMSO-d6) 10.5 +q), 11.3 +q), 51.6 +q), 55.8
+q), 107.4 +s), 114.4 +d), 116.1 +s), 121.5 +d), 132.4 +s),
133.7 +s), 136.9 +s), 155.6 +s), 157.6 +s), 163.8 +s), 165.7
+s); MS: m/z +%) 360+30) [M 1], 317 +5), 238 +100). Anal.
Calcd for C17H20N4O5: C, 56.66; H, 5.59; N, 15.55. Found:
C, 56.81; H, 5.41; N, 15.61.
4.4.12. Compound 14l. White powder from ethyl acetate/
petroleum ether +40±608C); mp 180±1838C; IR: nmax 3290,
1735, 1705, 1655 cm21; dH +DMSO-d6) 1.36 +9H, s, CO2t-
Bu), 2.37 +3H, s, CH3), 3.66 +3H, s, CO2CH3), 6.97 +1H, t,
Jˆ7.6 Hz, aromatic), 7.24 +2H, t, Jˆ7.6 Hz, aromatic),
7.30±7.42 +5H, m, aromatic), 7.56 +2H, d, Jˆ7.6 Hz,
aromatic), 10.13 +1H, s, NH, D2O exch.), 10.41 +1H, s,
NH, D2O exch.); dC +DMSO-d6) 10.9 +q), 28.5 +q), 51.6
+q), 81.6 +s), 108.6 +s), 119.3 +s), 119.8 +d), 123.5 +s),
128.7 +d), 129.1 +d), 130.0 +d), 132.0 +s), 136.9 +s), 140.4
+s), 155.0+s), 164.2 +s), 164.4 +s); MS: m/z +%) 449 +7)
[M1], 357 +47), 349 +100). Anal. Calcd for C25H27N3O5:
C, 66.80; H, 6.05; N, 9.35. Found: C, 66.72; H, 6.12; N,
9.24.
4.4.8. Compound 14h. White powder from ethyl acetate/
petroleum ether +40±608C); mp 236±2388C; IR: nmax 3305,
3220, 1730, 1675, 1625 cm21; dH +DMSO-d6) 2.16 +3H, s,
CH3), 2.33 +3H, s, CH3), 3.64 +3H, s, CO2CH3), 3.70+3H, s,
OCH3), 6.85 +2H, d, Jˆ8.4 Hz, aromatic), 6.98 +1H, t,
Jˆ7.6 Hz, aromatic), 7.27 +2H, t, Jˆ7.6 Hz, aromatic),
7.45 +2H, d, Jˆ7.6 Hz, aromatic), 7.60+2H, d, Jˆ8.4 Hz,
aromatic), 9.30+1H, s, NH, D O exch.), 9.50+1H, s, NH,
2
D2O exch.), 10.06 +1H, s, NH, D2O exch.); dC +DMSO-d6)
10.5 +q), 11.4 +q), 51.6 +q), 55.8 +q), 107.7 +s), 114.3 +d),
116.3 +s), 119.5 +d), 121.3 +d), 129.4 +d), 132.2 +s), 133.8 +s),
136.8 +s), 139.8 +s), 154.4 +s), 155.6 +s), 163.9 +s), 165.2 +s);
MS: m/z +%) 436 +25) [M1], 404 +14), 328 +56), 314 +100).
Anal. Calcd for C23H24N4O5: C, 63.29; H, 5.54; N, 12.84.
Found: C, 63.38; H, 5.61; N, 12.71.
4.5. General procedure for the synthesis of 4-methoxy-
1H-pyrazol-5ꢀ2H)-ones 16a±c
To polymer-bound 1,2-diaza-1,3-butadienes 5g±h in THF
+7 ml) sodium methoxide +2 equiv.) was added under
magnetic stirring. The reaction was allowed to stand at
room temperature for 3±5 h obtaining 16a±c in solution
+.9±42%). The resin was washed with MeOH, THF and
DCM +3£5 ml) and the reaction mixture was acidi®ed by
addition of tri¯uoroacetic acid +1 equiv.). After evaporation
of the washing solvents under reduced pressure products
16a±c were obtained by crystallization from ethyl acetate/
petroleum ether +40±608C). The ®nal products 16a±c were
compared with authentic specimens by means of chromato-
graphic and spectroscopic techniques +TLC, IR, NMR,
MS).15
4.4.9. Compound 14i. White powder from ethyl acetate/
petroleum ether +40±608C); mp 208±2108C; IR: nmax
3340, 3155, 1745, 1690, 1655 cm21; dH +DMSO-d6) 1.37
+9H, s, CO2t-Bu), 2.12 +3H, s, CH3), 2.30+3H, s, CH 3), 3.64
+3H, s, CO2CH3), 3.71 +3H, s, OCH3), 6.86 +2H, d,
Jˆ8.4 Hz, aromatic), 7.57 +2H, d, Jˆ8.4 Hz, aromatic),
10.00 +1H, s, NH, D2O exch.), 10.71 +1H, br s, NH, D2O
exch.); dC +DMSO-d6) 10.2 +q), 11.0 +q), 28.4 +q), 51.7 +q),
55.8 +q), 81.8 +s), 107.9 +s), 114.4 +d), 116.7 +s), 121.5 +d),
131.3 +s), 133.6 +s), 135.9 +s), 155.7 +s), 156.4 +s), 163.6 +s),
165.3 +s); MS: m/z +%) 417 +21) [M1], 361 +11), 345 +5), 317
+16), 295 +18), 239 +100). Anal. Calcd for C21H27N3O6: C,
60.42; H, 6.52; N, 10.07. Found: C, 60.55; H, 6.41; N, 10.15.
4.5.1. Compound 16a. White powder from ethyl acetate/
petroleum ether +40±608C); mp 131±1328C; IR: nmax 3360,
3080, 1690, 1625, 1560 cm21; dH +DMSO-d6) 2.08 +3H, s,
CH3), 3.66 +3H, s, OCH3), 7.78 and 8.22 +2H, 2 s, NH2, D2O
exch.), 11.34 +1H, br s, NH, D2O exch.); dC +DMSO-d6) 9.0
4.4.10. Compound 14j. White powder from ethyl acetate/

5862
O. A. Attanasi et al. / Tetrahedron 57 12001) 5855±5863
+q), 60.0 +q), 126.8 +s), 140.4 +s), 149.2 +s), 157.3 +s); MS:
m/z +%) 177 +19) [M1], 128 +100). Anal. Calcd for
C6H9N3O3: C, 42.11; H, 5.30; N, 24.55. Found: C, 42.31;
H, 5.37; N, 24.41.
+s), 164.0+s); MS: m/z +%) 352 +50) [M1], 259 +100). Anal.
Calcd for C18H16N4O2S: C, 61.35; H, 4.58; N, 15.90. Found:
C, 61.42; H, 4.52; N, 15.82.
4.6.3. Compound 18c. Yellow powder from methanol; mp
169±1708C; IR: nmax 3200, 3140, 1690, 1680, 1590 cm21
;
4.5.2. Compound 16b. White powder from ethyl acetate/
petroleum ether +40±608C); mp 158±1608C; IR: nmax 3200,
1730, 1640, 1570 cm21; dH +DMSO-d6) 2.14 +3H, s, CH3),
3.72 +3H, s, OCH3), 7.12 +1H, t, Jˆ7.6 Hz, aromatic), 7.37
+2H, t, Jˆ7.6 Hz, aromatic), 7.54 +2H, d, Jˆ7.6 Hz,
dH +DMSO-d6) 1.47 +9H, s, CO2t-Bu), 2.28 +3H, s, CH3),
7.48±7.53 +3H, m, aromatic), 7.89±7.95 +2H, m, aromatic),
10.04 +1H, s, NH, D2O exch.), 11.95 +1H, br s, NH, D2O
exch.); dC +DMSO-d6) 16.5 +q), 28.0+q), 80.0+s), 104.5 +s),
125.8 +d), 129.3 +d), 131.1 +d), 132.6 +s), 150.4 +s), 153.3 +s),
165.4 +s), 166.4 +s); MS: m/z +%) 333 +20) [M1], 277 +100).
Anal. Calcd for C16H19N3O3S: C, 57.64; H, 5.74; N, 12.60.
Found: C, 57.52; H, 5.82; N, 12.72.
aromatic), 11.20+1H, s, NH, D O exch.), 12.01 +1H, br s,
2
NH, D2O exch.); dC +DMSO-d6) 9.0+q), 60.2 +q), 119.9 +d),
123.9 +d), 126.6 +s), 129.1 +d), 136.9 +s), 141.3 +s), 146.3 +s),
157.5 +s); MS: m/z +%) 247 +14) [M1], 128 +100). Anal.
Calcd for C12H13N3O3: C, 58.29; H, 5.30; N, 16.99.
Found: C, 58.41; H, 5.28; N, 16.78.
Acknowledgements
4.5.3. Compound 16c. Yellow powder from ethyl acetate/
petroleum ether +40±608C); mp 119±1218C; IR: nmax 3440,
1760, 1690, 1590 cm21; dH +DMSO-d6) 1.47 +9H, s, CO2t-
Bu), 2.04 +3H, s, CH3), 3.63 +3H, s, OCH3), 10.31 +1H, br s,
NH, D2O exch.); dC +DMSO-d6) 9.5 +q), 27.6 +q), 60.0 +q),
83.6 +s), 127.8 +s), 143.0+s), 146.7 +s), 157.9 +s); MS: m/z
+%) 228 +11) [M1], 128 +100). Anal. Calcd for C10H16N2O4:
C, 52.62; H, 7.07; N, 12.27. Found: C, 52.68; H, 7.18; N,
12.21.
This investigation was supported by the ®nancial assistance
Á
from the Universita degli Studi di Urbino and Consiglio
Nazionale delle Ricerche +CNR-Roma).
References
1. +a) Gordon, E. M.; Kerwin, Jr., J. F. Combinatorial Chemistry
and Molecular Diversity in Drug Discovery; Wiley:
Weinheim, 1998. +b) Terrett, N. K. Combinatorial Chemistry;
Oxford University: Oxford, 1998. +c) Brown, A. R.;
Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. C.
Synlett 1998, 817±827. +d) Jung, G. Combinatorial Chemistry;
Wiley: Weinheim, 1999. +e) James, I. W. Tetrahedron 1999,
4.6. General procedure for the synthesis of 2-thiazolin-4-
ones 18a±c
To polymer-bound 1,2-diaza-1,3-butadienes 5f±h in MeOH
+7 ml) thiobenzamide +10equiv.) was added, under
magnetic stirring. The reaction was allowed to stand at
room temperature for 2±3 h obtaining 18a±c in solution
+.11±42%). The resin was washed with MeOH, THF and
DCM +3£5 ml) and the solvent was removed in vacuo and
the 2-thiazolin-4-ones 18a±c were puri®ed by chroma-
togaphy separation on a silica gel column +elution with
ethyl acetate±cyclohexane mixtures). The ®nal products
18a±c were compared with authentic specimens by means
of chromatographic and spectroscopic techniques +TLC, IR,
NMR, MS).16
È
55, 4855±4946. +f) Dorner, B.; Steinauer, R.; White, P.
Chimia 1999, 53, 11±17. +g) Seneci, P. Solid Phase Synthesis
and Combinatorial Technologies; Wiley: New York, 2000.
È
+h) Zaragoza Dorwald, F. Organic Synthesis on Solid Phase;
Wiley: Weinheim, 2000.
2. +a) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. C.
Tetrahedron 1996, 52, 4527±4554. +b) Hermkens, P. H. H.;
Ottenheijm, H. J. C.; Rees, D. Tetrahedron 1997, 53, 5643±
5678. +c) Booth, S.; Hermkens, P. H. H.; Ottenheijm, H. C. J.;
Rees, D. C. Tetrahedron 1998, 54, 15385±15443.
3. +a) Tietze, L. F.; Steinmetz, A. Angew. Chem., Int. Ed. Engl.
1996, 35, 651±652. +b) Tietze, L. F.; Steinmetz, A. Synlett
1996, 667±668. +c) Tietze, L. F.; Hippe, T.; Steinmetz, A.
Synlett 1996, 1043±1044. +d) Tietze, L. F.; Steinmetz, A.;
Balkenhohl, F. Bioorg. Med. Chem. Lett. 1997, 7, 1303±
1306. +e) Tietze, L. F.; Hippe, T.; Steinmetz, A. Chem.
Commun. 1998, 793±794.
4.6.1. Compound 18a. Orange powder from methanol; mp
173±1748C; IR: nmax 3300, 3150, 1700, 1680, 1650, 1610,
1560cm 21; dH +DMSO-d6) 2.27 +3H, s, CH3), 6.27 +2H, br
s, NH2, D2O exch.), 7.47±7.50+3H, m, aromatic), 7.86±7.90
+2H, m, aromatic), 9.30+1H, br s, NH, D O exch.), 11.68
2
+1H, br s, NH, D2O exch.); dC +DMSO-d6) 15.8 +q), 107.0
+s), 125.9 +d), 129.4 +d), 131.3 +d), 133.0+s), 147.0+s), 153.5
+s), 163.1 +s), 164.6 +s); MS: m/z +%) 276 +30) [M1], 232
+100). Anal. Calcd for C12H12N4O2S: C, 52.16; H, 4.38; N,
20.28. Found: C, 52.22; H, 4.42; N, 20.32.
4. +a) Attanasi, O. A.; Caglioti, L. Org. Prep. Proc. Int. 1986, 18,
299±327. +b) Attanasi, O. A.; Filippone, P. Synlett 1997,
1128±1140.
5. +a) Banert, K. Targets in Heterocyclic SystemsÐChemistry
Á
and Properties; Attanasi, O. A., Spinelli, D., Eds.; Societa
4.6.2. Compound 18b. Yellow powder from methanol; mp
188±1898C; IR: nmax 3360, 3200, 1685, 1675, 1600,
1590cm 21; dH +DMSO-d6) 2.34 +3H, s, CH3), 7.00 +1H, t,
Jˆ7.6 Hz, aromatic), 7.30+2H, t, Jˆ7.6 Hz, aromatic),
7.50±7.58 +5H, m, aromatic), 7.91±7.94 +2H, m, aromatic),
8.65 +1H, s, NH, D2O exch.), 9.68 +1H, s, NH, D2O exch.),
11.79 +1H, s, NH, D2O exch.); dC +DMSO-d6) 15.5 +q),
107.8 +s), 119.6 +d), 123.0 +d), 126.3 +d), 129.4 +d), 130.0
+d), 131.5 +d), 133.4 +s), 139.7 +s), 145.7 +s), 153.7 +s), 162.9
Chimica Italiana: Rome, 2000; Vol. 3, p. 1, Chapter 1.
+b) Polanc, S. Targets in Heterocyclic SystemsÐChemistry
Á
and Properties; Attanasi, O. A., Spinelli, D., Eds.; Societa
Chimica Italiana: Rome, 2000; Vol. 3, Chapter 2 and
references cited therein.
6. +a) Ferguson, G.; Lough, A. J.; Mackay, D.; Weeratunga, G. J.
Chem. Soc., Perkin Trans. 1 1991, 3361±3369. +b) Avalos,
Â
M.; Babiano, R.; Cintas, P.; Jimenez, J. L.; Molina, M. M.;
Â
Palacios, J. C.; Sanchez, J. B. Tetrahedron Lett. 1991, 32,

O. A. Attanasi et al. / Tetrahedron 57 12001) 5855±5863
5863
2513±2516. +c). Gilchrist, T. L.; Lemos, A. J. Chem. Soc.,
Perkin Trans. 1 1993, 1391±1395. +d) South, M. S.;
Jakuboski, T. L.; Westmeyer, M. D.; Dukesherer, D. R.
J. Org. Chem. 1996, 61, 8921±8934.
9. Witzeman, J. S.; Nottingham, W. D. J. Org. Chem. 1991, 56,
1713±1718.
10. +a) Visweswariah, S.; Prakash, G.; Bhushan, V.; Chandrasekaran,
S. Synthesis 1982, 309±310. +b) Attanasi, O. A.; Filippone, P.;
Mei, A.; Serra-Zanetti, F. J. Heterocycl. Chem. 1985, 22, 1341±
1343. +c) Attanasi, O. A.; Filippone, P.; Guerra, P.; Serra-Zanetti,
F. Synth. Commun. 1987, 17, 555±561. +d) Attanasi, O. A.;
Grossi, M.; Mei, A.; Serra-Zanetti, F. Org. Prep. Proc. Int.
1988, 20, 405±408. +e) Dauben, W. G.; Warshawsky, A. M.
Synth. Commun. 1988, 18, 1323±1326. +f) Jacques, J.; Marquet,
A. Org. Synth. Coll. 1988, 6, 175. +g) Attanasi, O. A.; Filippone,
P.; Guidi, B.; Perrulli, F. R.; Santeusanio, S. Heterocycles 1999,
51, 2423±2430.
7. +a) Arcadi, A.; Attanasi, O. A.; De Crescentini, L.; Rossi, E.
Tetrahedron Lett. 1997, 38, 2329±2332. +b) Attanasi, O. A.;
Filippone, P.; Fiorucci, C. Tetrahedron 1997, 53, 1467±1480.
+c) Attanasi, O. A.; De Crescentini, L.; Foresti, E.; Gatti, G.;
Giorgi, R.; Perrulli, F. R.; Santeusanio, S. J. Chem. Soc.,
Perkin Trans. 1 1997, 1829±1835. +d) Attanasi, O. A.;
Filippone, P.; Fiorucci, C.; Mantellini, F. Synlett 1997,
1361±1362. +e) Attanasi, O. A.; Filippone, P.; Fiorucci, C.;
Foresti, E.; Mantellini, F. J. Org. Chem. 1998, 63, 9880±9887.
+f) Arcadi, A.; Attanasi, O. A.; Guidi, B.; Rossi, E.;
Santeusanio, S. Chem. Lett. 1999, 59±60. +g) Attanasi, O. A.;
De Crescentini, L.; Filippone, P.; Perrulli, F. R.; Santeusanio,
S. Synlett 1999, 339±341. +h) Attanasi, O. A.; Filippone, P.;
Fiorucci, C.; Mantellini, F. Tetrahedron Lett. 1999, 40, 3891±
3894. +i) Attanasi, O. A.; De Crescentini, L.; Filippone, P.;
Guidi, B.; Perrulli, F. R.; Santeusanio, S. Synlett 1999, 1367±
1370. +j) Arcadi, A.; Attanasi, O. A.; Guidi, B.; Rossi, E.;
Santeusanio, S. Eur. J. Org. Chem. 1999, 3117±3126.
+k) Attanasi, O. A.; Filippone, P.; Foresti, E.; Guidi, B.;
Santeusanio, S. Tetrahedron 1999, 55, 13423±13444.
11. Attanasi, O. A.; Filippone, P.; Mei, A. Tetrahedron 1992, 48,
1707±1714.
12. Frenette, R.; Friesen, R. W. Tetrahedron Lett. 1994, 49, 9177±
9180.
13. Attanasi, O. A.; Filippone, P.; Mei, A.; Santeusanio, S.
Synthesis 1984, 671±672.
14. Attanasi, O. A.; Filippone, P.; Mei, A.; Santeusanio, S.
Synthesis 1984, 873±874.
15. Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Foresti, E.;
Galeazzi, R.; Ghiviriga, I.; Katritzky, A. R. Tetrahedron 1997,
53, 5617±5640.
16. Attanasi, O. A.; De Crescentini, L.; Foresti, E.; Galarini, R.;
Santeusanio, S.; Serra-Zanetti, F. Synthesis 1995, 1397±1400.
8. Attanasi, O. A.; Filippone, P.; Guidi, B.; Hippe, T.; Mantellini,
F.; Tietze, L. F. Tetrahedron Lett. 1999, 40, 9277±9280.